Suppressor T cell memory. Induction and recall of HGG-specific memory suppressor T cells and their role in regulation of antibody production.

Regulation of the antibody response to the hapten, dinitrophenyl (DNP), was studied using human gammaglobulin (HGG) as the carrier in an adoptive transfer system. CBA mice immunized at least 4 weeks previously to HGG or DNP served as the source of T helper cells and hapten-primed B cells, respectively. The addition of spleen cells from donors recently primed to HGG in immunogenic form (aHGG) suppressed the collaborative anti-DNP PFC response as effectively as cells from tolerant donors. The suppressive effect was antigen-specific and was mediated by a T cell with the same phenotype (Ly-1-, Ly-23+, Ia+) and induction kinetics as those previously identified in HGG-tolerant animals. During the primary response to HGG an early burst of helper activity was detected initially, followed by a wave of suppression which peaked at day 7 and subsequently waned, allowing adoptive helper function to reappear during the third week. When previously immunized animals were boosted with soluble HGG after primary suppression had waned, the sequential appearance of helper and suppressor activity was accelerated, and the secondary suppressive effect was more profound and of longer duration than that observed during a primary response. Although helper activity was not apparent during the peak of secondary suppression, helper T cells (Th) had not been functionally deleted since treatment of the donor spleen cells with anti-Ia and complement to deplete suppressor T cells (Ts) before adoptive transfer resulted in significant augmentation of the anti-DNP response. The secondary suppressive effect was formally shown to be mediated by activated Ts effector cells bearing the same surface markers as the cells responsible for primary suppression. The results suggest that the Ts population, like other lymphocyte subsets, contain memory cells capable of rapid reexpression of effector function upon secondary exposure to antigen. These cells are considered to be of a major importance in maintenance of immune homeostasis.